What is Epigenomics?

What makes them different?

Much human variation is due to difference in ~6 million DNA base pairs (0.1% of genome)

  • Phenotype, including disease susceptibility
  • One led a fairly strict diet and regimen, had pancreatic cancer, the other did not
  • While that gives a lot of information about the molecular basis of certain processes, it is not the full story.

What makes them different?

Genes are expressed differently during different stages and in different tissues.

  • Something that we want to understand is how that genetic variation leads to phenotypic variation.
  • A major part of understanding that, comes from understanding how regulation works.

DNA is packed, making certain parts inaccessible, and this packing is dynamic.

  • DNA structure plays a major role

DNA methylation is a chemical modification of DNA, involved in gene expression regulation.

[Robertson and Wolffe, Nat Rev Genet, 2000]
  • DNA methylation plays a major role in this regulation process
  • Plus, we know how it is inherited from cell to cell, cell-fate
  • invovled in differentiation
  • can give us an important idea of this process in development and disease
  • plasticity

Probing DNA Methylation

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Probing DNA Methylation

Nature Genetics, 2011Bioinformatics, 2013

DNA Methylation in cancer

Large blocks of *hypo-methylation in colon cancer

Nat. Genetics, 2011
  • long,
  • consistent but partially methylated in normal tissues
  • while methylation levels are inconsistent in cancer, boundaries of these domains are conserved across tissues

Genes with hyper-variable expression in colon cancer are enriched within these blocks.

Nat. Genetics, 2011

Hypo-methylation blocks observed in other cancer types.

Genome Medicine, 2014

Gene expression hyper-variability enriched in hypo-methylation blocks in other cancer types.

Genome Medicine, 2014

BMC Bioinformatics, 2013

Genes with consistent hyper-variable expression across tumors are tissue-specific.

Summary


Genes are expressed differently during different stages and in different tissues.